The origin of As enrichments in groundwater of many parts of the world is poorly understood. The problem is particularly acute in Bangladesh where 120 million people draw their drinking water from about 4 million wells that tap into aquifers of the Ganges-Brahmaputra Delta. It is estimated that approximately two thirds of these wells supply water containing >50 mug/L As, the current EPA limit. The situation, distressing as it is, provides a special opportunity to study dose-response relationships in humans. One difficulty of such a study is the extreme spatial variability of As concentrations in groundwater of Bangladesh. It also is not known to what extent there are temporal variations in groundwater As. The first objective of this project is therefore to collect detailed time series of groundwater As concentrations in the region where biomedical Project 3 and 4 will be conducted over a period of 4 years. The second objective is to use this information to test several hypotheses that have been proposed to explain the extremely wide range of As concentrations in groundwater in Bangladesh. An improved understanding of the still largely unknown geochemical and hydrological factors that regulate As levels in groundwater will be directly transferable to the many parts of the US where groundwater is enriched in As due to either natural processes or anthropogenic inputs (Projects 5 and 7). Our working hypothesis is that As is mobilized and re-concentrated in different sediment layers through a series of oxidation and reduction reactions that do not proceed at the same rate for As and for Fe. Under certain conditions, such a sequence could lead to extremely high As levels in groundwater. This hypothesis, and others that have been proposed, will be tested with multi-disciplinary study of the hydrology, geophysics, and geochemistry of the region where the biomedical studies will be conducted. The overall groundwater flow regime will first be determined from a broad survey of geophysical properties and hydrologic tracers such as 3H, 3He, and 14C. On the basis of this information, six new multi- level wells will be installed an approximately 15 existing drinking water wells spanning a range of redox conditions will be monitored intensively. In addition to As concentrations and speciation, the suite of parameters to be measured in the wells will include hydraulic head temperature, conductivity, Ph, Eh, dissolved O2, NO3, Mn, Fe, SO4, 18O and D(2H).